Maternal and Fetal Response to Fetal Persistent Infection with Bovine Viral Diarrhea Virus*

Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
American Journal Of Reproductive Immunology (Impact Factor: 2.44). 10/2010; 64(4):295-306. DOI: 10.1111/j.1600-0897.2010.00904.x
Source: PubMed


Infection of naïve pregnant cows with non-cytopathic (ncp) bovine viral diarrhea virus (BVDV) results in transplacental infection of the fetus. Infection of the pregnant cow with ncp BVDV late in gestation (after day 150) results in transient infection (TI), as both the dam and fetus can mount an immune response to the virus. In contrast, if the fetus is infected with ncp BVDV early in gestation (before day 150), the fetal immune system is undeveloped and unable to recognize the virus as foreign. This results in induction of immune tolerance to the infecting BVDV strain and persistent infection (PI).
Infection of naïve pregnant heifers with ncp BVDV2 on day 75 was hypothesized to induce differential gene expression in white blood cells of the dams and their fetuses, adversely affecting development and antiviral immune responses in PI fetuses.
Gene expression differed in maternal blood cells in the presence of PI versus uninfected fetuses. PI adversely affected fetal development and antiviral responses, despite protective immune responses in the dam.
Fetal PI with BVDV alters maternal immune function, compromises fetal growth and immune responses, and results in expression of maternal blood biomarkers that can be used to identify cows carrying PI fetuses.

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Available from: Andrey Ptitsyn, Oct 21, 2014
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    • "In PI cattle, the immunological tolerance to the persistent virus is highly specific, and CD4+ T-cells from PI cattle challenged with a heterologous virus can recognize single amino acid differences between the challenge and persistent virus [66]. In pregnant heifers carrying a PI fetus, the expression of IFN-stimulated gene 15kd following BVDV infection was considerably lower than in heifers pregnant with a transiently infected fetus [67]. Furthermore, prolonged downregulation of chemokine receptor 4 and T cell receptor pathways was observed in blood of cattle pregnant with a PI fetus [68]. "
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    ABSTRACT: Infections with bovine viral diarrhea virus (BVDV) of the genus pestivirus, family Flaviviridae, are not limited to cattle but occur in various artiodactyls. Persistently infected (PI) cattle are the main source of BVDV. Persistent infections also occur in heterologous hosts such as sheep and deer. BVDV infections of goats commonly result in reproductive disease, but viable PI goats are rare. Using 2 BVDV isolates, previously demonstrated to cause PI cattle and white-tailed deer, this study evaluated the outcome of experimental infection of pregnant goats. Pregnant goats (5 goats/ group) were intranasally inoculated with BVDV 1b AU526 (group 1) or BVDV 2 PA131 (group 2) at approximately 25-35 days of gestation. The outcome of infection varied considerably between groups. In group 1, only 3 does became viremic, and 1 doe gave birth to a stillborn fetus and a viable PI kid, which appeared healthy and shed BVDV continuously. In group 2, all does became viremic, 4/5 does aborted, and 1 doe gave birth to a non-viable PI kid. Immunohistochemistry demonstrated BVDV antigen in tissues of evaluated fetuses, with similar distribution but reduced intensity as compared to cattle. The genetic sequence of inoculated viruses was compared to those from PI kids and their dam. Most nucleotide changes in group 1 were present during the dam's acute infection. In group 2, a similar number of mutations resulted from fetal infection as from maternal acute infection. Results demonstrated that BVDV may cause reproductive disease but may also be maintained in goats.
    Full-text · Article · Apr 2014 · Veterinary Research
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    • "These fetuses become persistently infected (PI) and then shed the virus postnatally throughout their lifetime, thereby infecting other animals in the herd. Only one confi rmed maternal blood marker for PI fetuses during gestation has been described (Hansen et al., 2010); PI calves mostly appear normal and can be identifi ed only through detection of BVDV in tissues with concurrent lack of detection of antibodies against BVDV. Many PI fetuses have restricted growth in utero (Smirnova et al., 2008), which diminishes neonatal growth, weaning weight, and resistance to disease. "

    Full-text · Article · Apr 2013 · Journal of Animal Science
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    • "Another question is whether the expression of ISGs is induced by IFNτ or viral infection. ISGs respond to signals from the conceptus and from viruses, such as the bovine viral diarrhea virus (BVDV), which causes infectious diarrhea and mucosal disease in calves [35,36]. It is difficult to eliminate the effects of BVDV infection on the expression of ISGs following the start of conception. "
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    ABSTRACT: Background In food production animals, especially cattle, the diagnosis of gestation is important because the timing of gestation directly affects the running of farms. Various methods have been used to detect gestation, but none of them are ideal because of problems with the timing of detection or the accuracy, simplicity, or cost of the method. A new method for detecting gestation, which involves assessing interferon-tau (IFNT)-stimulated gene expression in peripheral blood leukocytes (PBL), was recently proposed. PBL fractionation methods were used to examine whether the expression profiles of various PBL populations could be used as reliable diagnostic markers of bovine gestation. Methods PBL were collected on days 0 (just before artificial insemination), 7, 14, 17, 21, and 28 of gestation. The gene expression levels of the PBL were assessed with microarray analysis and/or quantitative real-time reverse transcription (q) PCR. PBL fractions were collected by flow cytometry or density gradient cell separation using Histopaque 1083 or Ficoll-Conray solutions. The expression levels of four IFNT-stimulated genes, interferon-stimulated protein 15 kDa (ISG15), myxovirus-resistance (MX) 1 and 2, and 2′-5′-oligoadenylate synthetase (OAS1), were then analyzed in each fraction through day 28 of gestation using qPCR. Results Microarray analysis detected 72 and 28 genes in whole PBL that were significantly higher on days 14 and 21 of gestation, respectively, than on day 0. The upregulated genes included IFNT-stimulated genes. The expression levels of these genes increased with the progression of gestation until day 21. In flow cytometry experiments, on day 14 the expression levels of all of the genes were significantly higher in the granulocyte fraction than in the other fractions. Their expression gradually decreased through day 28 of gestation. Strong correlations were observed between the expression levels of the four genes in the granulocyte fractions obtained with flow cytometry and with density gradient separation. Conclusions The expression profiles of ISG15, MX1, MX2, and OAS1 could be a useful diagnostic biomarker of bovine gestation. Assessing the expression levels of these genes in a granulocyte fraction obtained with density gradient separation is a practical way of detecting gestation in cows within three weeks of insemination.
    Full-text · Article · Feb 2013 · Reproductive Biology and Endocrinology
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